It is proposed that continuous infusion, dual label tracer techniques and animal (rat) experimentation be utilized to study the sources of metabolic carbon flow under various conditions. The lactate fraction (i.e., lactate production rate/glucose + glycogen removal rates) is proposed as a means to study tissue "anaerobiosis" under various conditions (exercise, hypoxia, iron deficiency). The supposed effects of endurance training on free fatty acid and amino acid metabolism shall be quantified and related to glucose and glycogen metabolism (sparing) during prolonged exercise. The mechanism of the glucose + glycogen sparing effect of enhanced lipid oxidation in trained individuals shall be investigated. It is proposed that glycolytic derivatives play anaplerotic or cataplerotic, as well as substrate, roles supporting TCA cycle activity and fat oxidation during prolonged exercise. Following exhausting exercise, muscle glycogen levels are severely depleted. However, cardiac (completely) and skeletal muscle (partially) glycogen levels are replenished in starved animals. The precursor of this repletion is not glycolytic, but amino acids and/or glycerol are proposed as the major sources. The major portion of all O2 consumed is linked to energy transductions of mitochondria, but the relationships among factors affecting VO2 at various organizational levels are poorly understood. We propose to study these relationships utilizing several methods to increase or compromise VO2max. VO2max will be manipulated by exercise training, dietary iron deficiency and repletion, and erythrocyte removal and boosting. Maximal rates of O2 utilization wil be measured in sub-mitochondrial particles and mitochondria from skeletal muscle, in muscle homogenates, and intact animals. We shall partition the various effects of circulatory and local factors determining Vo2max and endurance. This partitioning of effects can be accomplished not only because we have the technical capacity to manipulate blood 02 carrying capacity and tissue respiratory capacity, but also because we can determine cardiac output (direct Fick method) and blood flow distribution (microsphere method).